Acute Myeloid Leukemia
Conditions
Keywords
Pharmacokinetics, Venetoclax, Pharmacodynamics, Cytologic response, Azole antifungal
Brief summary
This is a prospective, multicenter, clinical-biological cohort study. Its objective is to assess the pharmacokinetics-pharmacodynamics (PK-PD) of venetoclax (VEN) in patients with Acute Myeloid Leukemia (AML). This study involves only minimal risks and constraints related to the collection of biological samples (blood samples for PK testing) and the collection of clinical data. Therapeutic management of patients participating in this study is not changed. A total of 100 patients will be included in the study over a 12-month period. A maximum of 21 additional samples are planned, with a maximum of 12 mL of blood per sampling day (4 mL at each sampling time) for PK dosing of venetoclax.
Interventions
OTHERPharmacokinetic dosages of venetoclax
Blood samples for pharmacokinetic dosing of venetoclax at different endpoints of treatment period
Sponsors
Centre Leon Berard
Fédération Leucémie Espoir
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Clinical-biological cohort
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patient aged of at least 18 years on day of signing informed consent * Patient with histologically-confirmed diagnosis of Acute Myeloblactic Leukaemia according to classification ELN 2022 (European Leukemia Net 2022) * Patient who has to initiate treatment venetoclax-azacitidine as first line. Note : triple associations with targeted therapy are not authorized * Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed. * Patient must be affiliated or benificiary of a social security system.
Exclusion criteria
* Patient with acute promyelocytic leukemia (APL, AML3) * Patient with AML eligible to intensive chemotherapy * Patient previously treaed with venetoclax and/or azacitidine * Patient participating to another clinical trial with a medicinal product * Any condition that contraindicates blood sampling procedures required by the protocol * Any psychological, family, geographical, or social situation that, according to investigator's judgment, could potentially prevent the signing of an informed consent form and/or woulld likely interfere compliance with study procedures. * Patient under curatorship, guardianship or judicial protection * Pregnant or breast-feeding female patient.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best pharmacokinetic (PK) indicator of response to treatment in patients with AML - Biological endpoint | From the first day of venetoclax administration to end of the treatment (days) | To assess PK exposure parameters : AUC (area under the curve) of venetoclax at steady state |
| Best pharmacokinetic (PK) indicator of response to treatment in patients with AML - Clinical Endpoint | From the first day of venetoclax administration up to day 28 (end of the first venetoclax cure) | Proportion of patients with a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) or partial remission (PR) or no remission |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess relationship between different PK markers of venetoclax and its clinical efficacy. | From the first day of venetoclax administration and through study completion, at least 24 months | Correlation between PK exposure parameters (including Cmin, Cmax, Css) of venetoclax and clinical outcome (cytologic response at cycle 6, survival without progression and overall survival). |
| To assess correlation between plasmatic exposition to venetoclax and occurrence of adverse events | From the the first day of venetoclax administration to the last day (Day 168) of venetoclax administration | Correlation between PK exposure parameters (including Cmin, Cmax, Css) of venetoclax and occurence of adverse events grade equal or superior to 3 related to venetoclax/azacitidine and their impact on treatment administration |
| To assess inter-individual and intra-individual variability in plasma exposure to venetoclax. | From the first day of ventoclax administration and nd through study completion, at least 24 months | Coefficient of variation of AUC and Cmin at steady state for venetoclax |
Countries
France
Contacts
CONTACTMichaël Philippe
CONTACTAmine Belhabri, MD
Outcome results
None listed